1. Field of the Invention
The present invention relates to a water-soluble binder. More particularly, the invention relates to a water-soluble binder which can be mixed with various active ingredients and such mixtures can be molded into various shapes to provide unit dosage forms. When such unit dosage forms are placed in water, the binder dissolves in the water at a certain rate while constantly releasing the active ingredient.
In the following description and claims, the term "unit dosage form" means a physically discrete solid shape containing a predetermined quantity of one or more active ingredients effective for treating a material to obtain a beneficial result, but excluding the therapeutic treatment of human beings and animals. In addition to the active ingredients, the unit dosage form contains a water-soluble binder and various optional materials such as fillers, perfumes, coloring agents and the like.
2. Description of the Prior Art
As water-soluble binder bases for unit dosage forms, there have heretofore been used, for example, polyethylene glycol having a molecular weight of from 1,000 to 6,000, polypropylene glycol having a molecular weight of from 1,000 to 6,000, mixtures thereof, and water-soluble high-melting-point nonionic surface active agents which are solid at normal ambient temperature.
When these substances are used as binders, they become swollen when they are immersed in water for a long time, surface portions thereof are dissolved away in the slurry state and the active components are released into the water at a rapid rate. Accordingly, it is impossible to maintain a constant rate of release of the active components over a long time period and, therefore, the desired action of the active ingredient cannot last for a long time. In short, they have the disadvantage that the rate of release of the active components changes depending on the length of time that the unit dosage form has been in contact with water. Moreover, some of the previously used binders readily foam or bubble when they are placed in water and these bubbles persist for a long time. This bubbling action is not wanted in some applications.
The present invention overcomes the foregoing disadvantages of the conventional binders.
It is a principal object of the present invention to provide a binder which has a property such that when a unit dosage form containing the binder and one or more active ingredients is placed in water, the active components are not released at an excessively rapid rate and do not completely dissolve in a short time, but rather, they are released into the water at a substantially constant rate over a long period of time, whereby the activities of the active components can be maintained at predetermined levels for a long time. The binder has a much lower tendency to bubble and it can be used with a variety of active components.
More specifically, in accordance with the present invention, there is provided a water-soluble binder comprising, as a main component, a product obtained by condensing a polyoxyethylene alkyl, alkylphenyl or alkenyl ether having the following formula (I): EQU r--o--ch.sub.2 ch.sub.2 o).sub.n H (I)
wherein R is alkyl or alkenyl having 8 to 22 carbon atoms or alkylphenyl having 8 to 22 carbon atoms in the alkyl group, and n is an integer of from 50 to 500, with 1-epoxyethyl-3,4-epoxycyclohexane having the following formula (II): ##STR2## wherein the molar ratio of the compound of the formula (II) to the compound of the general formula (I) is in the range of from 0.05/1.0 to 2.5/1.0.
The condensation product of the formula (I) compound and the formula (II) compound (which condensation product is hereinafter sometimes referred to as "PAEH"), that is used as the main component of the binder of the present invention, can be obtained by a process comprising blowing ethylene oxide into a higher alcohol or alkylphenol of the formula ROH, wherein R has the same meaning as defined above, at about 100.degree. C., in the presence of an alkali catalyst such as NaOH or KOH, whereby to add a predetermined amount of ethylene oxide to the higher alcohol or alkylphenol to form the formula (I) substance, adding a predetermined amount of 1-epoxyethyl-3,4-epoxycyclohexane of the above formula (II) dropwise to the resulting formula (I) adduct over a period of 1 to 3 hours in the presence of an alkali catalyst such as those mentioned above, and conducting the reaction for several hours. After completion of the reaction, the reaction product is neutralized with an appropriate acid, such as acetic acid, whereby to obtain PAEH used in the present invention.
The water-solubility of the binder of the present invention can be changed by varying the molar ratio of the formula (II) compound to the formula (I) compound in the PAEH used as the main component, and also by varying the carbon number of R in the formula (I) and the mole number "n" of added ethylene oxide. In order to attain the object of the present invention, it is critical that the molar ratio of 1-epoxyethyl-3,4-epoxycyclohexane of the formula (II) to the polyoxyethylene alkyl, alkenyl or alkylphenyl ether of the formula (I) should be in the range of from 0.05/1.0 to 2.5/1.0, preferably in the range of from 0.2/1.0 to 0.7/1.0. As this molar ratio becomes higher, the water solubility of the PAEH product is decreased, and if this molar ratio exceeds 2.5, the water solubility is too low and good results cannot be obtained. Similarly, the alkyl, the alkenyl and the alkyl moiety of the alkylphenyl group, used as R in the formula (I) compound, have 8 to 22 carbon atoms, preferably 14 to 22 carbon atoms, and the mole number n of added ethylene oxide is in the range of from 50 to 500, preferably in the range of from 150 to 250.
The PAEH condensation product is heated and melted, optional additives such as an extender are added to the melt according to need, and then the active ingredient or ingredients, selected according to the intended purpose of the unit dosage form, are added and mixed in the melt. Then, the resulting homogeneous melt is cooled to room temperature and is thereby solidified or the melt is molded into any desireable unit dosage form shape and is solidified. Alternatively, the melt is cast into a mold having an appropriate shape and is cooled and solidified. Thus, a unit dosage form containing the water-soluble binder of the present invention is formed.
The water-soluble binder of the present invention can be molded into any suitable unit dosage form shape containing therein various active components. When the unit dosage form is placed into water or aqueous liquids, the contained active components are gradually released at substantially constant rates over a long period of time. Accordingly, the active components are selected appropriately, depending on the intended purpose of use of same, so that the water-soluble binder of the present invention can be used in various fields. Some examples of applications of the water-soluble binder of the present invention are as follows: